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Review
. 2016 May;101(5):521-30.
doi: 10.3324/haematol.2015.132860.

Nonmyeloablative allogeneic hematopoietic cell transplantation

Rainer Storb  1 , Brenda M Sandmaier  2
Affiliations
Review

Nonmyeloablative allogeneic hematopoietic cell transplantation

Rainer Storb et al. Haematologica. 2016 May.

Abstract

Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease.

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Figures

Figure 1.
Figure 1.
Reproduced from: Sandmaier BM, Storb R. Reduced-intensity allogeneic transplantation regimens, Chapter 21, In: Thomas’ Hematopoietic Cell Transplantation, 5th Edition. Forman SJ, Negrin RS, Antin JH, and Appelbaum FR, Eds., ©John Wiley & Sons, Ltd., in press.
Figure 2.
Figure 2.
Five-year relapse mortality and overall survival of patients with advanced hematologic malignancies who were conditioned with FLU/2 Gy TBI before HLA-matched related or unrelated HCT and postgrafting immunosuppression with MMF/calcineurin inhibitor. Survival is shown depending on relapse risk and hematopoietic comorbidity scores (HCT-CI).
Figure 3.
Figure 3.
Overall survival. (A) The probability of OS by donor type after myeloablative conditioning regimen, adjusted for age and disease risk index. (B) The probability of OS by donor type after reduced intensity conditioning regimen, adjusted for disease risk index and secondary AML. (Originally published in Blood. Ciurea SO, Zhang MJ, Bacigalupo AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs. matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033–1040. ©The American Society of Hematology).
Figure 4.
Figure 4.
Graft-versus-host disease and use of systemic steroids. (A) Cumulative incidence of use of systemic steroids in arm 1 (n=69), arm 2 (n=71) and arm 3 (n=68). (B) Viral infections. Cumulative incidence of cytomegalovirus reactivation in arm 1 (n=69), arm 2 (n=71) and arm 3 (n=68). Originally published in Haematologica (Kornblit B, et al. A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation. Haematologica 2014; 99(10): 1624–1631. ©2014 Ferrata Storti Foundation).
See this image and copyright information in PMC

References

    1. Yu C, Storb R, Mathey B, et al. DLA-identical bone marrow grafts after low-dose total body irradiation: Effects of high-dose corticosteroids and cyclosporine on engraftment. Blood. 1995;86(11):4376–4381. - PubMed
    1. Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997;89(8):3048–3054. - PubMed
    1. Hogan WJ, Little M-T, Zellmer E, et al. Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates. Biol Blood Marrow Transplant. 2003;9(8):489–495. - PubMed
    1. Storb R, Yu C, Barnett T, et al. Stable mixed hematopoietic chimerism in dog leukocyte antigen-identical littermate dogs given lymph node irradiation before and pharmacologic immunosuppression after marrow transplantation. Blood. 1999;94(3):1131–1136. - PubMed
    1. Appelbaum FR, Brown P, Sandmaier B, et al. Antibody-radionuclide conjugates as part of a myeloblative preparative regimen for marrow transplantation. Blood. 1989;73(8): 2202–2208. - PubMed

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